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Case Details

An 80 –year-old man presented with impairment of brain functions, alterations of mood and behavior.His family reported that he was having progressive disorientation and memory loss over the past 6 months.  He had trouble handling money and paying bills. He repeated questions, took longer to complete normal daily tasks, had poor judgment, and had developed mood and personality changes.

There was no family history of dementia.The routine blood, urine and C.S.F analysis did not reveal much.After a computerized tomography (CT) scan and the histopathological examination of the brain tissue, the patient was diagnosed to be having Alzheimer disease.

What is the defect in this disease?

How is the diagnosis done and what is its prognosis?

Case discussion

Alzheimer’s disease

Basic Concept

Alzheimer’s disease is defined as premature aging of the brain, usually beginning in mid-adult life and progressing rapidly to extreme loss of mental powers—similar to those, seen in very, very old age.

Clinical features

Alzheimer’s disease is a progressive and fatal neurodegenerative disorder that results in impairment of a person” ability to perform routine activities and the patient finally enters in to a vegetative state with no comprehension to the outside world. The disease runs in four stages, pre dementia. Mild dementia, moderate dementia and advanced dementia.

Although the course of Alzheimer’s disease is unique for every individual, there are many common symptoms.

The earliest observable symptoms are often mistakenly thought to be ‘age-related’ concerns, or manifestations of stress. In the early stages, the most commonly recognized symptom is memory loss, such as difficulty in remembering recently learned facts.

As the disease advances, symptoms include confusion, irritability and aggression, mood swings, language breakdown, long-term memory loss, and the general withdrawal of the sufferer as their senses decline.

Gradually, bodily functions are lost, ultimately leading to death.


 Alzheimer’s disease is the most common form of dementia in the elderly and about 5 million people in the United States are estimated to be afflicted by this disorder. The percentage of persons with Alzheimer’s disease approximately doubles with every five years of age, with about 1 percent of 60-year-old and about 30 percent of 85-year-olds having the disease.

Biochemical defect

Alzheimer’s disease has been identified as a protein misfolding disease, caused by accumulation of abnormally folded A-beta and tau proteins in the brain. Plaques are made up of small peptides, 39–43 amino acids in length, called beta-amyloid (also written as A-beta or Aβ). Beta-amyloid is a fragment from a larger protein called amyloid precursor protein (APP), a transmembrane protein that penetrates through the neuron’s membrane.

APP is critical to neuron growth, survival and post-injury repair.

 In Alzheimer’s disease, an unknown process causes APP to be divided into smaller fragments by enzymes through proteolysis. One of these fragments gives rise to fibrils of beta-amyloid, which form clumps that deposit outside neurons in dense formations known as senile plaques.(Figure-1)

AD is also considered a tauopathy due to abnormal aggregation of the tau protein. Every neuron has a cytoskeleton, an internal support structure partly made up of structures called microtubules. These microtubules act like tracks, guiding nutrients and molecules from the body of the cell to the ends of the axon and back. A protein called tau stabilizes the microtubules when phosphorylated, and is therefore called a microtubule-associated protein. In AD, tau undergoes chemical changes, becoming hyperphosphorylated; it then begins to pair with other threads, creating neurofibrillary tangles and disintegrating the neuron’s transport system.

Amyloid plaques and Neuro fibrillary tangles

Figure-1 -showing amyloid plaques and Neuro fibrillary tangles in Alzheimer disease

AD, is also associated with a decrease in the cerebral cortical levels of several proteins and neurotransmitters, especially acetyl choline; there is reduction in nor epinephrine levels also in brain stem nuclei.

ApoE 4 allele has a strong association with AD in the general population, ApoE is present in the neuritic amyloid plaques of AD, and it may also be involved in neurofibrillary tangle formation, because it binds to tau protein.

Accumulation of aggregated amyloid fibrils, which are believed to be the toxic form of the protein responsible for disrupting the cell’s calcium ion homeostasis, induces programmed cell death (apoptosis). Aβ selectively builds up in the mitochondria in the cells of Alzheimer’s-affected brains, and it also inhibits certain enzyme functions and the utilization of glucose by neurons.

Brain atrophy in Alzheimer's disease

Figure-2 showing brain atrophy


The vast majority of cases of Alzheimer’s disease are sporadic, meaning that they are not genetically inherited although some genes may act as risk factors. On the other hand around 0.1% of the cases are familial forms of Autosomal-dominant inheritance, which usually have an onset before age 65.

The best known genetic risk factor is the inheritance of the ε4 allele of the Apo lipoprotein E (APOE). Between 40 and 80% of patients with AD possess at least one apoE4 allele. The APOE4 allele increases the risk of the disease by three times in heterozygotes and by 15 times in homozygotes


Alzheimer’s disease is usually diagnosed clinically from the patient’s history, collateral history from relatives, and clinical observations, based on the presence of characteristic neurological and neuropsychological features and the absence of alternative conditions.

Assessment of intellectual functioning including memory testing can further characterize the state of the disease.

Advanced medical imaging with computed tomography (CT) or magnetic resonance imaging (MRI), and with single photon emission computed tomography (SPECT) or positron emission tomography (PET) can be used to help exclude other cerebral pathology or subtypes of dementia.

Alzheimer’s disease is characterized by loss of neurons and synapses in the cerebral cortex and certain sub cortical regions. This loss results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus.(Figure-2) Studies using MRI and positron emission tomography have documented reductions in the size of specific brain regions in patients as they progressed from mild cognitive impairment to Alzheimer’s disease, and in comparison with similar images from healthy older adults.

A histopathological confirmation including a microscopic examination of brain tissue is required for a definitive diagnosis. Both amyloid plaques and neurofibrillary tangles are clearly visible by microscopy in brains of those afflicted by AD.(Figure-1)


There is no cure for Alzheimer’s disease; available treatments offer relatively small symptomatic benefit but remain palliative in nature. Current treatments can be pharmaceutical, psychosocial and care giving.

Four medications are approved by the U.S. Food and Drug Administration to treat AD. Donepezil, rivastigmine, and galantamine) are used to treat mild to moderate AD (Donepezil can be used for severe AD as well). Memantine is used to treat moderate to severe AD. These drugs work by regulating neurotransmitters. They may help maintain thinking, memory, and speaking skills, and help with certain behavioral problems. However, these drugs don’t change the underlying disease process and may help only for a few months to a few years.


Individual prognosis is difficult to assess, as the duration of the disease varies. AD develops for an indeterminate period of time before becoming fully apparent, and it can progress undiagnosed for years. The mean life expectancy following diagnosis is approximately seven years. The earlier the age at onset the higher the total survival years, life expectancy is part Men have a less favorable survival prognosis than women.

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